title: Ki67 measured after neoadjuvant chemotherapy for primary breast cancer.
abstract: OBJECTIVE
  The value of Ki67 measured on residual disease after neoadjuvant chemotherapy is not sufficiently described.
  
  
  METHODS
  Participants of the GeparTrio study with primary breast cancer randomly received neoadjuvant response-guided [8 cycles TAC (docetaxel/doxorubicin/cyclophosphamide) in responding and TAC-NX (vinorelbine/capecitabine) in nonresponding patients] or conventional (6 cycles TAC) chemotherapy according to interim response assessment. Ki-67 levels were centrally measured immunohistochemically after neoadjuvant treatment if tumor tissue was available. Here, we analyze 1,151 patients having a pathologic complete response (pCR; n, 484), or residual disease with low (0-15%), intermediate (15.1-35%), or high (35.1-100%) posttreatment Ki67 levels in 488, 77, and 102 patients, respectively.
  
  
  RESULTS
  Patients with high posttreatment Ki67 levels showed higher risk for disease relapse (P < 0.0001) and death (P < 0.0001) compared with patients with low or intermediate Ki67 levels. Patients with low Ki67 levels showed a comparable outcome to patients with a pCR (P = 0.211 for disease-free and P = 0.779 for overall survival). Posttreatment Ki67 levels provided more prognostic information than pretreatment Ki67 levels or changes of Ki67 from pre- to posttreatment. Information on pCR plus posttreatment Ki67 levels surmount the prognostic information of pCR alone in hormone-receptor-positive disease [hazard ratios (HR), 1.82-5.88] but not in hormone-receptor-negative disease (HR: 0.61-1.73). Patients with conventional and response-guided treatment did not show a different distribution of posttreatment Ki67 (P = 0.965).
  
  
  CONCLUSIONS
  Posttreatment Ki67 levels provide prognostic information for patients with hormone-receptor-positive breast cancer and residual disease after neoadjuvant chemotherapy. Levels were not prognostic for outcome after response-guided chemotherapy. High posttreatment Ki67 indicates the need for innovative postneoadjuvant treatments.
authors.affiliation: German Breast Group, Neu-Isenburg, Germany. gunter.vonminckwitz@germanbreastgroup.de
authors.forename: Gunter
authors.initials: G
authors.lastname: von Minckwitz
authors.forename: Wolfgang D
authors.initials: WD
authors.lastname: Schmitt
authors.forename: Sibylle
authors.initials: S
authors.lastname: Loibl
authors.forename: Berit M
authors.initials: BM
authors.lastname: Müller
authors.forename: Jens U
authors.initials: JU
authors.lastname: Blohmer
authors.forename: Bruno V
authors.initials: BV
authors.lastname: Sinn
authors.forename: Holger
authors.initials: H
authors.lastname: Eidtmann
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Eiermann
authors.forename: Bernd
authors.initials: B
authors.lastname: Gerber
authors.forename: Hans
authors.initials: H
authors.lastname: Tesch
authors.forename: Jörn
authors.initials: J
authors.lastname: Hilfrich
authors.forename: Jens
authors.initials: J
authors.lastname: Huober
authors.forename: Tanja
authors.initials: T
authors.lastname: Fehm
authors.forename: Jana
authors.initials: J
authors.lastname: Barinoff
authors.forename: Thomas
authors.initials: T
authors.lastname: Rüdiger
authors.forename: Erhard
authors.initials: E
authors.lastname: Erbstoesser
authors.forename: Peter A
authors.initials: PA
authors.lastname: Fasching
authors.forename: Thomas
authors.initials: T
authors.lastname: Karn
authors.forename: Volkmar
authors.initials: V
authors.lastname: Müller
authors.forename: Christian
authors.initials: C
authors.lastname: Jackisch
authors.forename: Carsten
authors.initials: C
authors.lastname: Denkert
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D016896:Treatment Outcome; D047368:Tumor Burden; D055815:Young Adult
chemical_list: D019394:Ki-67 Antigen